Translated by Dr. Taigo Kato
For the first time in three years, I recently delivered a public lecture at my previous workplace, the Institute of Medical Science at the University of Tokyo. The last time was right before I left Japan and moved to Chicago in 2012. The time has flown by since then, and it seems the older one gets the faster time seems to go. I think this is because 1 year is 1/10th of life for 10 year-old children, but only 1/60th of life for 60 year-olds like me.
Every time I go back to Japan, I have opportunities to talk with many people. In conversations I have always stressed the vital importance of issues such as the Japanese drug trade deficit, delays in the development of medical devices, and the slow pace of introducing personalized medicine strategies for cancer patients. Lately, however, I am getting tired of talking about these issues because I feel there is a gap between these people and me. While I always emphasize these issues in my lectures, I feel I am the only one who is struggling to understand and address these challenges.
When it comes to racing marathons, runners are usually motivated to speed up when they can see the front runners just ahead of them. On the other hand, runners can feel irritated and incompetent when the front runners are too far ahead of them. Comparing the pace of engagement with these critical issues in medicine between Japan and the U.S., Japan’s pace is lagging, not even at the half-way point, while the U.S is running well, completing maybe 80% of the course so far. Japan cannot see any of the front runners at all and has lost its spirit, plodding along with clumsy feet. I also wonder if I am similarly only at the half way point in my research.
Moreover, I think Japanese bureaucrats and politicians don’t even want to see or understand the front runner’s position. In the field of medicine, “Black Ships” (symbols of urgent issues to be addressed) are seen already in Uraga Bay. However, Japanese bureaucrats and politicians ignore them with impunity and continue living in their self-satisfied and insular small worlds.
In my recent lecture in Japan, I discussed the system of personalized medicine in France. The French government introduced the system to select patients to have drug administration by checking the absence or presence of the genetic mutation of patients’ cancer cells. If ineffective drugs are administered to patients, it could lead to cancer progression. And needless to say, the cost of the medications would be wasted. For example, molecularly-targeted drugs affect only patients who have mutations in specifically targeted molecules.
This French system is very effective because you can maintain the quality of medicine and suppress medical costs at the same time. Japan faces a critically urgent crisis in drug development and use, nevertheless its top leaders cannot decide whether to establish this kind of system. They have not developed an effective national policy on the question. Normally, the Ministry of Health, Labor and Welfare or National Cancer Center should lead on this. But they can’t do that because top-down strategically-driven decision making has not been incorporated throughout Japanese culture. This obstruction has blocked innovative change and Japan has therefore not been able to move forward.
Japan can’t catch up with evolving methods for clinical trials
In addition to these policy-related problems, Japan also doesn’t respond well to rapid changes in clinical trial methodologies to test molecularly-targeted drugs. In Japan, some clinical oncologists still insist to perform randomized trials. Usually in clinical randomized trials to evaluate the effect of new drugs, patients are divided into a group trying the new drug vs an observation group, or a group trying the new drug plus conventional drugs vs a group using conventional drugs only.
At the University of Chicago, I have been on the committee for clinical trials for almost 2 years. Usually, clinical trials consist of 3 Phases before Federal approval of a new drug is granted: Phase 1 is mainly screening for safety; Phase 2 establishes the efficacy of the drug, usually against a placebo; and Phase 3 is a final confirmation of safety and efficacy. In the case where a new drug’s beneficial effect is clear and convincing, they are sometimes approved without a Phase 3 trial. This is particularly relevant in rare cancers, where new drugs are often approved when they have excellent efficacy compared to conventional drugs.
When molecularly targeted drugs demonstrate a very high degree of efficacy in Phase 1, investigators can often switch to Phase 2 without much interruption or the need for randomization. If the targeted tumor shrinks in, say, 6 out of 20 patients and completely diminishes in 2 out of 20 patients, many committee members think that it may be unethical to withhold such promising treatment to a new group of patients in the placebo arm of a Phase 2 trial. In contrast, research committees in Japan tend to avoid these essential discussions with an endless emphasis on procedures and practice enshrined in bureaucrats’ rulebooks. Many Japanese committee members tend to cling to these formalities without accounting for the importance of “moral principles.”
In these situations, I think the best strategy is to fill the gaps of knowledge between patients, medical staff and advanced researchers. Contrasting clinical information with genome-specific information, it is important to construct systems where medical treatment information should be combined with other information, such as genomic information. This approach would facilitate the blossoming of personalized medicine, where effective treatments with fewer side effects are brought to bear on the suffering of our patients.
In upcoming columns, I would like to talk about issues in clinical care settings caused by the above mentioned knowledge gaps, and argue for the importance of big data.